Ventilation-perfusion mismatching in chronic obstructive pulmonary disease during ventilator weaning

Using the multiple inert gas elimination technique, we studied ventilation-perfusion (VA/Q) relationships in eight patients with chronic obstructive pulmonary disease (COPD) during mechanical ventilation (MV) and again during weaning (spontaneous ventilation [SV] through an endotracheal tube) from MV needed for acute respiratory failure. The patients, seven men and one woman with a mean age of 63 +/- 2.8 (SEM) yr (FEV1 33 +/- 5.2% of predicted), required MV for 9.0 +/- 2.4 days prior to the study. The patients were studied at maintenance FIO2 (0.28 to 0.40) while breathing 100% O2, both during MV and SV. After 30 min of SV, PaCO2 increased from 48.9 +/- 3.4 to 58.3 +/- 3.1 mm Hg (p = 0.003) and pH decreased from 7.42 +/- 0.01 to 7.36 +/- 0.01 (p = 0.001) without significant changes in PaO2. Despite a decrease in tidal volume (VT) from 700.0 +/- 41.1 during MV to 313.0 +/- 39.6 ml during SV (p = 0.001), minute ventilation remained unchanged (from 8.2 +/- 0.7 during MV to 7.4 +/- 0.6 L/min during SV). Furthermore, cardiac output (QT), oxygen delivery (QO2), and mixed venous PO2 (PVO2) significantly rose during SV when compared with the MV (QT: from 4.7 +/- 0.4 to 6.7 +/- 0.7 L/min, p = 0.011; QO2: from 857.3 +/- 113.0 to 1078.5 +/- 158.9 ml/min, p = 0.0074; PVO2: from 36.7 +/- 1.1 to 42.3 +/- 2.2 mm Hg, p = 0.041). Overall VA/Q inequality worsened as blood flow was redistributed to low VA/Q areas (from 9.4 +/- 4.4 to 19.6 +/- 5.3% of QT, p = 0.05). The dispersion of the ventilation distribution (log SDV) significantly worsened during SV (from 1.0 +/- 0.08 during MV to 1.2 +/- 0.08 during SV, p = 0.044). No changes were observed in either series dead space or ventilation of high VA/Q ratio units.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of almitrine on ventilation-perfusion distribution in adult respiratory distress syndrome

Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q mismatching is the cause of severe hypoxemia, are not known. The effects of almitrine on pulmonary gas exchange and circulation were assessed in 9 patients with ARDS who were sedated, paralyzed, and mechanically ventilated at constant FlO2 (range, 0.48 to 0.74). Systemic and pulmonary hemodynamics, conventional gas exchange, and the VA/Q distribution by the multiple inert gas elimination technique (MIGT) were measured before (baseline), during (ALM 15), at the end of (ALM 30), and at 30-min intervals after (POSTALM 30, 60, and 90) the intravenous infusion of 0.5 mg/kg body weight of almitrine over 30 min. Almitrine significantly increased PaO2 from 78 +/- 15 mm Hg to 140 +/- 49 at ALM 15 and 138 +/- 52 at ALM 30. AaPO2 and QS/QT decreased during the administration of the drug. The MIGT showed that almitrine redistributed pulmonary blood flow from shunt areas (reduction from 29 +/- 11 to 17 +/- 11% of QT) to lung units with normal VA/Q ratios (increase from 63 +/- 9 to 73 +/- 6% of QT). The Ppa increased from 26 +/- 5 to 30 +/- 5 mm Hg without changes in QT. Changes were transient, returning toward baseline 30 min after stopping the infusion of the drug. Almitrine significantly reduced the VA/Q inequalities present in ARDS and may be useful in the management of those patients.     

Hemodynamic disturbances and VA/Q matching in hypoxemic cirrhotic patients

Arterial oxygen desaturation is commonly found in patients with cirrhosis of the liver, but severe hypoxemia is unusual. To investigate the mechanism of the impairment in gas exchange, six severely hypoxemic (mean PaO2, 55.9 +/- 5.9 mm Hg) cirrhotic patients (five confirmed by biopsy), without pulmonary or cardiovascular disease and in the absence of acute hepatic disease, were submitted to right heart catheterization. Inequalities of VA/Q were estimated in the respiratory steady state using the multiple inert gas technique. The mean pulmonary arterial pressure was low (7.2 +/- 2.3 mm Hg) and the cardiac output high (Q = 11.0 +/- 2.06 L/min), indicating a low PVR. The VA/Q mismatching of the ventilated and perfused units ranged from mild to moderate, but a large percentage of Q flowed through unventilated areas. Furthermore, there was a significant difference between predicted and measured PaO2 (9.27 +/- 5.9 mm Hg; p less than 0.01), which was attributed to either an unmeasured postpulmonary shunt (between portal and pulmonary vein) or a diffusion defect. The impairment in gas exchange in these patients is thus due primarily to an intrapulmonary, and possibly extrapulmonary, shunt. This was thought to be due mainly to an impaired regulatory mechanism of the microcirculation by the hepatic dysfunction.     

Pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis

To determine and to quantify the pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis, we measured in 10 cirrhotics blood gases, P50, hemodynamics, ventilation, and the distribution of ventilation-perfusion ratios (VA/Q) using the multiple inert gas elimination technique. Seven patients had an arterial hypoxemia (PaO2 = 69 +/- 6 mm Hg, mean +/- SD), and three patients were normoxemic (PaO2 = 89 +/- 6 mm Hg). In each hypoxemic patient, the VA/Q distributions were characterized by the presence of low VA/Q units. A negative logarithmic correlation was found between the dispersion of the blood flow distribution and the arterial PO2. An acute inspiratory hypoxia (FIO2, 0.125) elicited an increase in pulmonary vascular resistance by 58.5% in the hypoxemic group and by 81.6% in the normoxemic one (p = NS between the two groups). The percent change in pulmonary vascular resistance induced by hypoxia was not correlated with the percent change in the dispersion of the blood flow distribution. A theoretical analysis showed that the mean arterial PO2 of 69 mm Hg of the hypoxemic group differed from a normal reference value of 96 mm Hg as a result of the combined effects of reduced hemoglobin (-4 mm Hg), increased P50 (+4 mm Hg), increased ventilation (+10 mm Hg), low VA/Q (-35 mm Hg), and true shunt (-2 mm Hg). These results show that the "hypoxemia of liver cirrhosis" is essentially caused by VA/Q mismatching, which is not explained by an abnormal hypoxic pulmonary vasoconstriction.     

Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome

The mechanism of orthodeoxia (OD), or decreased partial pressure of arterial oxygen (PaO2) from supine to upright, a characteristic feature of hepatopulmonary syndrome (HPS), has never been comprehensively elucidated. We therefore investigated the intrapulmonary (shunt and ventilation-perfusion [VA/Q] mismatching) and extrapulmonary factors governing PaO2 in 20 patients with mild to severe HPS (14 males, 6 females; 50 +/- 3 years old SE) at upright and supine, in random order. We set out a cutoff value for OD, namely a PaO2 decrease > or = 5% or > or = 4 mm Hg (area under the receiver operating characteristic curve, 0.96 each). Compared to supine, 5 patients showed OD (PaO2 change, -11% +/- 2%, -7 +/- 1 mm Hg, P < .05) with further VA/Q worsening (shunt + low VA/Q mode increased from 19% +/- 7% to 21% +/- 7% of cardiac output [QT], P < .05), as opposed to 15 patients who did not (+2% +/- 2%, +1+/- 1 mm Hg) with VA/Q improvement (from 20% +/- 4% to 16% +/- 4% of QT, P < .01). Cardiac output was significantly lower in OD patients in both positions. Changes in extrapulmonary factors at upright, such as increased minute ventilation and decreased QT, were of similar magnitude in both subsets of patients. In conclusion, our data suggest that gas exchange response to OD in HPS points to a more altered pulmonary vascular tone inducing heterogeneous blood flow redistribution to lung zones with prominent intrapulmonary vascular dilatations.     

Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension is characterized by widespread central obstruction of the pulmonary arteries with organized thrombus and thereby differs substantially from other forms of pulmonary hypertension. We studied 25 patients using the multiple inert gas elimination technique to identify and quantitate the physiologic mechanisms of hypoxemia in this disorder. All patients had chronic obstruction of the central pulmonary arteries, which was demonstrated angiographically and later surgically confirmed. All patients but one were hypoxemic (PaO2 = 65 +/- 11 mm Hg, PaCO2 = 32 +/- 4 mm Hg, AaPO2 = 45 +/- 14 mm Hg), and all patients had pulmonary hypertension (mean Ppa = 45 +/- 11 mm Hg) with an elevated pulmonary vascular resistance (mean PVR = 1,000 +/- 791 dyne/s/cm5, normal less than 300). The cardiac index was reduced (1.7 +/- 0.6 L/min/m2), as was the P-vO2 (31 +/- 5 mm Hg). Inert gas studies revealed widened unimodal Va/Q distributions in 20 of 25 subjects, with a log standard deviation of 1.01 +/- 0.32 (upper limit of normal, 0.6; ages 20 to 40), shunt = 0.03 +/- 0.05 of cardiac output, and dead space of 3.4 +/- 1.1 ml/kg (upper limit of normal, 2.9). The VD/VT ratio was 0.51 +/- 0.10. No low (VA/Q less than 0.1) or high (VA/Q greater than 10.0) regions were present, and no evidence for diffusion limitation of O2 transfer at rest was found. The low cardiac output and resulting low P-VO2 were responsible for approximately 33% of the increased AaPO2. The magnitude of the VA/Q abnormality correlated poorly with the PVR, the mean Ppa, or the magnitude of vascular obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis

To investigate the mechanisms underlying abnormal gas exchange in liver cirrhosis, 15 patients were studied while breathing room air, 11% O2, and 100% O2 in random sequence. Under basal conditions, patients showed mild reductions from normal in systemic and pulmonary vascular resistance, normal PaO2 (mean, 92.5 +/- 2.5 mm Hg), mild hypocapnia (mean, 34 +/- 0.7 mm Hg), and a slightly right-shifted oxyhemoglobin dissociation curve (P50, 27.2 +/- 0.4 mm Hg; 2,3-DPG, 13.1 +/- 0.6 mumol/g). Using the multiple insert gas elimination technique, we found mild to moderate ventilation-perfusion (VA/Q) inequality with a mean of 5% (range, 0 to 20%) of cardiac output (QT) perfusing low VA/Q ratio (less than 0.1) areas but no shunt. Breathing 11% O2, there were significant increases in QT, pulmonary artery pressure, and vascular resistance, whereas no changes occurred in VA/Q distribution, and there was no evidence for alveolar-endcapillary diffusion limitation for O2. In contrast, after 100% O2 shunt developed and VA/Q relationships worsened without significant hemodynamic changes. Furthermore, patients with cutaneous spider nevi (n = 8) showed more hepatocellular dysfunction (lower prothrombin values), lower systemic and pulmonary vascular resistance, less hypoxic pulmonary vasoconstriction (HPV), lower PaO2, and more VA/Q mismatch than did those without spiders. Our results confirm, therefore, that HPV is not fully abolished, as previously described, in hepatic cirrhosis. However, those patients with more advanced hepatic disease exhibit inadequate pulmonary vascular tone, which increases VA/Q inequality and lowers PaO2.     

Effects of propranolol on arterial oxygenation and oxygen transport to tissues in patients with cirrhosis

Patients with cirrhosis may show ventilation-perfusion (VA/Q) inequality in the absence of any intrinsic heart or lung disease. However, the high cardiac output of cirrhosis generally prevents or minimizes the appearance of a severe degree of arterial hypoxemia. Propranolol has been used to reduce cardiac output and portal pressure in these patients. We wondered whether it might alter arterial oxygenation and reduce O2 transport to tissues. We studied eight patients (three women) 54 +/- 3 (SEM) yr of age before and after intravenous propranolol (0.1 mg/kg followed by 2 mg/h). Cardiac output (QT) fell from 7.8 +/- 0.7 to 6.0 +/- 0.7 L/min (p less than 0.05), and portal pressure was reduced (22 +/- 2 to 19 +/- 2 mm Hg, p less than 0.01). Arterial PO2 did not change (88 +/- 4 to 89 +/- 5 mm Hg) because the fall in mixed venous PO2 (43 +/- 1 to 40 +/- 1 mm Hg, p less than 0.01) that followed the lower QT was counterbalanced by a lower intrapulmonary shunt (multiple inert gas technique) (4 +/- 2 to 2 +/- 1%, p less than 0.05) and a shift of the VA/Q distributions toward a higher VA/Q ratio. Paralleling the fall in QT, oxygen transport to tissues (QO2) was reduced (19 +/- 2 to 14 +/- 1 ml/min/kg, p less than 0.01). However, O2 uptake (VO2) remained constant (3.4 +/- 0.2 to 3.6 +/- 0.2 ml/min/kg) because O2 extraction by the tissues increased appropriately (22 +/- 2 to 28 +/- 1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypoxemia in acute pulmonary embolism

Most patients with severe, acute pulmonary embolism (PE) have arterial hypoxemia. To further define the respective roles of ventilation to perfusion (VA/Q) mismatch and intrapulmonary shunt in the mechanism of hypoxemia, we used both right heart catheterization and the six inert gas elimination technique in seven patients with severe, acute PE (mean vascular obstruction, 55 percent) and hypoxemia (mean PaO2, 67 +/- 11 mm Hg). None had previous cardiopulmonary disease, and all were studied within the first ten days of initial symptoms. Increased calculated venous admixture (mean QVA/QT 16.6 +/- 5.1 percent) was present in all patients. The relative contributions of VA/Q mismatching and shunt to this venous admixture varied, however, according to pulmonary radiographic abnormalities and the time elapsed from initial symptoms to the gas exchange study. Although all patients had some degree of VA/Q mismatch, the two patients studied early (ie, less than 48 hours following acute PE) had normal chest x-ray film findings and no significant shunt; VA/Q mismatching accounted for most of the hypoxemia. In the others a shunt (3 to 17 percent of cardiac output) was recorded along with radiographic evidence of atelectasis or infiltrates and accounted for most of the venous admixture in one. In all patients, a low mixed venous oxygen tension (27 +/- 5 mm Hg) additionally contributed to the hypoxemia. Our findings suggest that the initial hypoxemia of acute PE is caused by an altered distribution of ventilation to perfusion. Intrapulmonary shunting contributes significantly to hypoxemia only when atelectasis or another cause of lung volume loss develops.     

The effects of changes of maternal PaO2 and PaCO2 on the fetal PaO2 and PaCO2--in vivo study

Umbilical PaO2 and PaCO2 were continuously monitored in vivo in acute fetal lamb preparations with a semipermeable membrane connected to a mass spectrometer. The response time of this system (0 to 90% of final value) was 36 sec. In seven pregnant sheep (128--135 days gestation) the maternal inspired mixture was abruptly changed and the following changes in fetal PaO2 and PaCO2 were observed: (1) 100% O2 to room air: PaO2 decreased from 21.5 +/- 0.8 (mean +/- SEM) to 14 +/- 1.1 mm Hg at a rate of 1.63 +/- 0.33 mm Hg/min. Following return to 100% O2 the PaO2 returned to 21 +/- 1.1 mm Hg at a rate of 2.44 +/- 0.4 mm Hg/min. (2) 100% O2 to 12% O2/10% CO2: after 6 min the PaO2 fell from 19.3 +/- 1.3 to 6.3 +/- 0.3 mm Hg at a rate of 4.65 mm Hg/min and the PaCO2 rose from 37 +/- 8 to 70 +/-5 mm Hg. At 100% O2 the PaO2 returned to 19 +/- 1.0 mm Hg at a rate of 11.76 +/- 0.086 mm Hg, the PaCO2 to 39 +/- 7 mm Hg. (3) 100% O2 to 90% O2/10% CO2. The PaO2 and PaCO2 increased by 4.7 and 22 mm Hg, respectively. The changes of fetal PaO2 and PaCO2 occurred after 1 minute of changing in maternal inspired mixture except in the transition from 12% O2/10% CO2 to 100% O2 (34 +/- 12 sec). Following the reinstitution of 100% the fetal PaO2 and PaCO2 returned to their previous values within 4 and 16 min, respectively.     

Gas exchange during maximal upper extremity exercise

STUDY OBJECTIVE: to characterize gas exchange and cardiopulmonary performance during maximal progressive arm crank exercise. DESIGN: Cardiopulmonary variables were measured and arterial blood gases were determined in blood samples obtained from an indwelling radial arterial catheter during arm crank exercise (34 watts/min). Arm crank exercise was compared to maximal leg exercise performed by a different but comparable group of subjects from a previous study. PARTICIPANTS: 19 healthy young (mean +/- SEM: 20 +/- 1 yr) black males. RESULTS: Peak arm crank exercise resulted in lower values compared to peak leg exercise for: power (129 +/- 2 vs 253 +/- 10 W), VO2 (2.17 +/- 0.04 vs 3.26 +/- 0.14 L/min); VCO2 (2.9 +/- 0.11 vs 4.32 +/- 0.17 L/min); HR (168 +/- 3 vs 189 +/- 3 beats/min); AT (1.15 +/- 0.05 vs 1.83 +/- 0.07 L/min); and VE (101 +/- 2 vs 144 +/- 8 L/min), respectively. Arm crank exercise (baseline vs peak) elicited an impressive improvement in PaO2 (85 +/- 1 to 97 +/- 1 mm Hg), no change in SaO2 (96 +/- 0.2 to 96 +/- 0.2 percent), no significant increase in P(A-a)O2 (3 +/- 0.7 to 5 +/- 0.9 mm Hg) and an appropriate trending decrease in VD/VT (0.22 +/- 0.01 to 0.17 +/- 0.01). Peak arm crank values were significantly different from peak cycle exercise for PaO2 (82 +/- 2.2 mm Hg), SaO2 (93 +/- 0.4 percent), P(A-a)O2 (21 +/- 1.9 mm Hg) and VD/VT (0.08 +/- 0.01). At comparable levels of VO2 for arm crank and cycle exercise (2.17 +/- 0.04 vs 2.26 +/- 0.08 L/min), significant differences were observed for PaO2 (97 +/- 1.4 vs 81 +/- 1.9 mm Hg); SaO2 (96 +/- 0.2 vs 94 +/- 0.4 percent); P(A-a)O2 (5 +/- 0.9 vs 14 +/- 1.5 mm Hg); and VD/VT (0.17 +/- 0.01 vs 0.08 +/- 0.01), respectively. CONCLUSIONS: Maximal arm crank exercise represents a submaximal cardiopulmonary stress compared to maximal leg exercise. The differences in gas exchange observed at peak exercise between arm crank and leg exercise for the most part reflect the lower VO2 achieved. However, the persistence of these gas exchange differences even at a comparable level of VO2 suggests that factors other than VO2 may be operative. These factors may include differences in alveolar ventilation, CO2 production, ventilation-perfusion inequality, diffusion, and control of breathing.     

Prediction of PaO2 during treadmill walking in patients with COPD

We studied the possibility of predicting PaO2 during exercise of a given oxygen uptake (VO2) from resting pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD). The three-minute incremental treadmill exercise was performed with serial measurements of PaO2 via intra-arterial catheter in 46 patients (mean FEV1 = 1.09 +/- 0.49L, mean FEV1/FVC = 44 +/- 15 percent). In most of the patients, the changes of PaO2 were quite linear in relation to the oxygen uptake, so a slope (PaO2/VO2) could be obtained from the regression equation in each patient. The mean value of the slope (SL) was -23.0 +/- 16.6 mm Hg/L VO2/min. Correlation between SL and all parameters of resting PFTs were computed. Because of the high correlation coefficient between SL and %DCO (SL = -59.3 + 0.501 X %DCO, r = 0.851, p less than 0.001), it was possible to predict PaO2 at a given VO2 using the following equation: PaO2 predicted = PaO2 rest + SL X (VO2 -0.25), where SL was derived from measured %DCO and resting VO2 was assumed 0.25 L/min. There was a high correlation between the predicted PaO2 at VO2 of 1.0 L/min and the estimated PaO2 obtained from individual PaO2 regression with an r value = 0.898 and SEE = +/- 5.8 mm Hg. A prospective study in 12 patients with COPD was then carried out. There was a high correlation (r = 0.857) between the predicted PaO2 obtained from the present equation and the estimated PaO2 at VO2 = 1.0 L/min. It was concluded that PaO2 during treadmill walking with a given oxygen uptake is predictable from a resting PaO2 and a diffusing capacity. This predicted value may be useful in the management of patients with COPD.     

Severe hypoxemia and liver disease

Severe hypoxemia and orthodeoxia in patients with chronic liver disease is uncommon, but, when present, it is incapacitating. The purpose of this study was to determine the distribution of alveolar ventilation-perfusion (VA/Q) in six patients with mild liver disease and severe hypoxemia (PaO2 at rest in sitting or standing position ranged from 35 to 67 mm Hg). Orthodeoxia was documented with improvement in PaO2 in the supine position in each patient (PaO2 at rest in supine position ranged from 46 to 75 mm Hg). VA/Q distribution was measured by the multiple inert gas elimination technique. The dispersion of VA/Q was increased with small portions of the cardiac output (0.5 to 14.8%) perfusing low VA/Q areas (O less than VA/Q less than 0.1). Another major finding was a large right-to-left shunt (VA/Q less than 0.005) that ranged from 4 to 28%. The VA/Q mismatching and the right-to-left shunt both contributed to the hypoxemia. The predicted PaO2 was 5.5 mm Hg (p less than 0.01) larger than the measured PaO2. In each patient, the mean pulmonary artery pressure was low and the cardiac output was elevated. These results show that the low PaO2 in these patients was due to both increased right-to-left shunt and VA/Q mismatching, but impaired diffusion could not be ruled out.     

Enhancement of hypoxic pulmonary vasoconstriction by almitrine in the dog

In order to test the hypothesis of enhancement of hypoxic pulmonary vasoconstriction by Almitrine, 12 anesthetized and paralyzed dogs with normal lungs were studied under controlled ventilation. They were ventilated in random sequence with air, 12% O2, and 100% O2, and almitrine (0.1 mg/kg body weight) was infused over 30 min during each O2 mixture. The multiple inert gas elimination technique was used to detect alterations in ventilation-perfusion (VA/Q) mismatching before and during the interventions and to measure cardiac output (QT). Arterial, mixed venous and expired gases, inert gas concentrations, and hemodynamic measurements were made while the dogs were breathing the different O2 mixtures before infusing the drug, near the end of 30 min of infusion and 30 min after infusion had ended. There were no significant changes in pH, PaO2, PaCO2, QT, oxygen uptake, oxygen delivery index, systemic vascular resistance, mean systemic arterial pressure, heart rate, stroke volume index, or VA/Q distribution during the experiment. Significant increases in: (a) pulmonary artery pressure (PA), (b) the pressure difference between PA and pulmonary capillary wedge pressure (PCw), and (c) pulmonary vascular resistance (PVR) occurred when the drug was infused during 12% O2 and air, but not during 100% O2. The PVR increased 59.7% with almitrine infusion during 12% O2 and 38.4% during air breathing (p less than or equal to 0.01), but there was no significant change during 100% O2. Vascular responses were not dependent on the order in which the different O2 mixtures were administered. These data strongly suggest that almitrine enhances hypoxic vasoconstriction in the lung, and this effect may explain reported improvement in PaO2 in hypoxic patients given the drug.     

Influence of cardiac output on oxygen exchange in acute pulmonary embolism.

We investigated interactions between cardiac output, VA/Q distribution pattern, pulmonary gas exchange, O2 transport, and tissue oxygenation in 16 patients during the acute phase of pulmonary embolism (PE). The effects of breathing room air, O2 therapy (FIO2 = 0.40) (11 patients), and dobutamine (four patients) were studied after right catheterization using the multiple inert gas elimination technique. The pattern of VA/Q ratio distributions was found to depend essentially on cardiac output level. The individual blood flow perfusing ventilated areas was found to be inversely related to the mean VA/Q ratio of blood flow distribution. PVO2 was directly related to cardiac index (p less than 0.02), and negatively related to the mean VA/Q of blood flow distribution. In view of the influence of low VA/Q ratios and PVO2 on arterial hypoxemia, our results showed that the heart's response to PE conditioned the strategy of pulmonary gas exchange and O2 transport. Oxygen breathing led to a slight but consistent fall in cardiac output (-0.6 +/- 0.5 L/min, p less than 0.01). However, although PaO2 remained normal and PVO2 was slightly improved, we found no evidence for a role of hypoxic pulmonary vasoconstriction in the pulmonary hypertension observed during the acute phase of PE. Administration of dobutamine improved O2 transport and tissue oxygenation, although PaO2 remained constant or even fell in some cases because of increased VA/Q mismatch.     

Use of arm crank exercise in the detection of abnormal pulmonary gas exchange in patients at low altitude.

BACKGROUND: The measurement of arterial blood gases, P(A-a)O2 and VD/VT, during cycle ergometry is the "gold standard" for the assessment of pulmonary gas exchange. However, some patients are unable to perform cycle ergometry because of other medical problems. STUDY OBJECTIVE: To determine whether arm crank exercise could be used to reliably detect gas exchange abnormalities compared to cycle ergometry. PARTICIPANTS: Fifteen patients with a variety of pulmonary disorders, who were referred for exertional dyspnea. DESIGN: All patients performed maximal arm crank and cycle exercise. Arterial blood gases, VO2, VCO2, and VE were measured at rest and during exercise. RESULTS: Compared to peak cycle exercise (mean +/- SD), PaO2 (85 +/- 14 vs 75 +/- 13 mm Hg), SaO2 (94 +/- 2 vs 91 +/- 4 percent), VD/VT (0.21 +/- 0.07 vs 0.19 +/- 0.08), and pH (7.37 +/- 0.04 vs 7.34 +/- 0.03) were significantly higher during peak arm crank exercise. The P(A-a)O2 (18 +/- 13 vs 29 +/- 12 mm Hg) was narrower, and PaCO2 (29 +/- 3 vs 29 +/- 4 mm Hg) and PAO2 (104 +/- 4 vs 103 +/- 4 mm Hg) were similar. Six patients had normal gas exchange during cycle exercise at low altitude (P[A-a]O2 less than or equal to 27 mm Hg, PaO2 greater than or equal to 65 mm Hg, VD/VT less than or equal to 0.18) and nine were abnormal. Utilizing criteria specific for arm crank at low altitude, the same six patients had normal gas exchange (P[A-a]O2 less than or equal to 13 mm Hg, PaO2 greater than or equal to 85 mm Hg, VD/VT less than or equal to 0.26), and the remaining nine were abnormal. The P(A-a)O2 during peak arm crank was the most useful criterion in identifying patients with abnormal gas exchange. CONCLUSION: Proposed criteria for arm crank exercise testing accurately identified all patients with normal and abnormal pulmonary gas exchange during cycle exercise. The data from the present study suggest that arm crank can be an acceptable alternative exercise testing modality for the assessment of pulmonary gas exchange.     

Arterial blood gas tension changes at the start of exercise in chronic obstructive pulmonary disease.

In a previously reported study of a group of normal subjects, large decreases in arterial O2 tension (PaO2) of as much as 37 mm Hg were measured during the first 90 sec of slow stair-climbing exercise (chosen as a common daily exertion). This study reports the changes in PaO2, arterial CO2 tension (PaCO2), and ventilation in 7 patients with chronic obstructive pulmonary disease and resting hypoxemia during the first 90 sec of similar exercise. The patient group showed significantly smaller unsteady-state decreases in PaO2 starting from a smaller resting value (patient group, 72 +/- 2.6 mm Hg, mean +/- SE; normal group, 92 +/- mm Hg; P less than 0.001) and decreasing to a similar smallest value (patient group, 58 +/- 3.8 mm Hg; normal group, 65 +/- 3.4 Hg; P greater than 0.05). PaCO2 tended to oscillate around the resting value in both the patient group and the normal group, and the rates of increase in ventilation in the 2 groups were similar. The physiologic processes that could limit the unsteady-state decrease in PaCO2 in the patient group are analyzed, the analysis suggesting that a slower rate of increase in tissue consumption of O2 is most likely to account for the smaller decrease in PaO2.     

Mechanical ventilation with 100% oxygen does not increase intrapulmonary shunt in patients with severe bacterial pneumonia

Pure oxygen ventilation has been shown to increase the right to left shunt QS/QT in both normal and diseased lungs. Nitrogen absorption atelectasis, an explanation of the phenomenon, is likely to occur in lung units with low ventilation/perfusion ratio. In 11 patients with severe unilateral or bilateral bacterial pneumonia, we assessed the effects of increasing FlO2 from maintenance level (m = 0.44 +/- 0.11) to 1.0. Venous admixture (QVA/QT) was calculated using the O2 method, and the distribution of the VA/Q ratios were assessed with the 6 inert gas (IG) technique providing the distribution between the true shunt (QS/QT IG) and the low VA/Q units. Although a large part of perfusion was distributed preferentially to low VA/Q units, ranging from 2 to 43% of cardiac output, thus placing large zones of lung parenchyma at risk of absorption atelectasis, QVA/QT decreased from 31 +/- 13% to 25 +/- 10% and IG shunt did not increase after 30 min of O2 ventilation. In addition, QS/QT IG remained unaltered despite PVO2 increased from 32 to 43 mmHg, suggesting a poor level of hypoxic vasoconstriction in human bacterial pneumonia.     

Ventilation-perfusion mismatch after methacholine challenge in patients with mild bronchial asthma

To investigate the effects of methacholine (MTH) challenge on spirometry, lung mechanics, respiratory gases, and ventilation-perfusion (VA/Q) distributions, 16 subjects 16 to 58 yr of age with stable mild asthma (FEV1, 92 +/- 5% [SEM] predicted; FEF25-75, 71 +/- 7% predicted; respiratory system resistance (Rrs) at 4 Hz, 4.6 +/- 0.4 cm H2O/L-1 s; PaO2, 88 +/- 3 mm Hg; AaPO2, 23 +/- 3 mm Hg) were recruited. Baseline VA/Q distributions were unimodal and relatively narrow in 12 patients and modestly bimodal in the other four. The dispersion of pulmonary blood flow (log SD Q) was slightly enlarged (0.71 +/- 0.09) and that of ventilation (log SD V) was normal (0.57 +/- 0.04) (normal range, 0.3 to 0.6); an index of overall VA/Q heterogeneity (DISP R-E*) was also mildly abnormal (5.3 +/- 0.8) (normal values less than 3.0). After MTH challenge, FEV1, FEF25-75, and PaO2 fell (to 62 +/- 3 and 35 +/- 3% predicted, and to 71 +/- 1 mm Hg, respectively), whereas Rrs (p less than 0.001 each), minute ventilation (p less than 0.02), heart rate (p less than 0.01), and AaPO2 increased (p less than 0.001). VA/Q relationships mildly to moderately worsened (log SD Q increased to 0.98 +/- 0.04 [p less than 0.01], log SD V to 0.79 +/- 0.04, and DISP R-E* to 9.8 +/- 0.6 [p less than 0.001 each]). Qualitatively, the pattern of blood flow distribution was broadly unimodal in 13 patients and modestly bimodal in three, of whom only one had a bimodal baseline distribution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of hydralazine on ventilation and blood gas values in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Hydralazine has been shown to increase minute ventilation, alveolar ventilation, and arterial partial pressure of oxygen (PaO2) after short-term administration in patients with chronic obstructive pulmonary disease and pulmonary hypertension. The effects of orally administered hydralazine on ventilation and blood gas values were evaluated after six to 18 months of treatment in 10 male patients who had demonstrated an increase in minute ventilation after 24 hours of treatment. Hydralazine was administered at a dose of 200 mg per day during the initial 24 hours and in doses ranging from 40 mg per day to 200 mg per day during long-term therapy. Following 24 hours of treatment, a statistically significant increase in minute ventilation, alveolar ventilation, and PaO2, and reduction in arterial partial pressure of carbon dioxide (PaCO2) were seen both at rest and during exercise. After six to 18 months of hydralazine therapy, the increase in minute ventilation at rest persisted when compared with the pre-hydralazine value (15.3 +/- 1.3 liters/minute versus 13.1 +/- 1.1 liters/minute; p less than 0.05). The improvement in PaO2 at rest continued relative to the pre-hydralazine value (70.9 +/- 3.2 mm Hg versus 65.1 +/- 3.0 mm Hg, p less than 0.05) as did the PaO2 during exercise (60.3 +/- 3.5 mm Hg versus 53.3 +/- 2.0 mm Hg; p less than 0.05). The reduction in PaCO2 at rest persisted compared with the pre-hydralazine value (41.2 +/- 2.4 mm Hg versus 47.0 +/- 3.0 mm Hg; p less than 0.05) as did the PaCO2 during exercise (44.0 +/- 2.8 mm Hg versus 48.0 +/- 2.8 mm Hg; p less than 0.05). No significant changes in minute ventilation, PaO2, or PaCO2 were seen at rest or during exercise, when re-measured after six to 18 months in an age- and sex-matched control group of 10 patients who did not receive hydralazine. These results demonstrate that the short-term effects of hydralazine on ventilation and blood gas values persisted after six to 18 months of treatment in this sample of patients, some of whom received doses less than 200 mg per day.